Different in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study

Background Conflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants. Methods The EPIC-InterAct case-cohort study includes 12¿403 people with incident type 2 diabetes and a representative subcohort of 16¿154 individuals who were selected from a cohort of 340¿234 European participants with 3·99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis. Findings SFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14:0 [myristic acid], 16:0 [palmitic acid], and 18:0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1·15 [95% CI 1·09–1·22], palmitic acid 1·26 [1·15–1·37], and stearic acid 1·06 [1·00–1·13]). By contrast, measured odd-chain SFAs (15:0 [pentadecanoic acid] and 17:0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0·79 [0·73–0·85] for pentadecanoic acid and 0·67 [0·63–0·71] for heptadecanoic acid), as were measured longer-chain SFAs (20:0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0·72 to 0·81 (95% CIs ranging between 0·61 and 0·92). Our findings were robust to a range of sensitivity analyses. Interpretation Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed. Funding EU FP6 programme, Medical Research Council Epidemiology Unit, Medical Research Council Human Nutrition Research, and Cambridge Lipidomics Biomarker Research Initiative

Dietary determinants, inflammation, and type 2 diabetes: insights from observational studies

Background Incidence of type 2 diabetes has rapidly increased during the last decades. It is a chronic disease caused by impaired insulin action and insulin secretion. Potentially, the majority of the new cases are due to changes in lifestyle, including unfavourable changes in diet. Lifestyle interventions promoting a healthy diet and physical activity indeed showed that diet has a role in the development of type 2 diabetes. However, firm conclusions about the role of most dietary factors and their association with type 2 diabetes cannot be drawn yet. Evidence for an association between a dietary factor and type 2 diabetes is strengthened when a potential pathway is elucidated through which a dietary factor can be linked to type 2 diabetes. Chronic low-grade inflammation may be one of these pathways. Elevated concentrations of C-reactive protein (CRP) and pro-inflammatory cytokines, like TNF-α and IL-6, have been associated with a higher risk of type 2 diabetes, at least through a connection with overweight and abdominal obesity. Whether chronic low-grade inflammation is an intermediate in the association between dietary factors and risk of type 2 diabetes is not often studied so far. Objectives The first objective of this thesis was to study the role of selected dietary factors, i.e., fatty acids, fish, tea, meat, glycemic index (GI), and glycemic load (GL), on the development of type 2 diabetes in observational studies. The second objective was to study the extent to which chronic low-grade inflammation is a pathway through which diet can affect the processes leading to type 2 diabetes. Methods Data were used from several ongoing prospective cohort studies, i.e., CODAM study, Rotterdam study, EPIC-InterAct study, and Hoorn study. In these studies, information about diet was collected with food frequency questionnaires. As a reflection of dietary fatty acid composition, the association between serum fatty acids in cholesteryl esters and glucose metabolism status was studied cross-sectionally in the CODAM study (n= 471). The prospective associations between fish (i.e., total, lean, fatty), meat (i.e., unprocessed red meat, processed red meat, poultry), GI, and GL and risk of type 2 diabetes were studied in the Rotterdam study (n= ≈4,400; nincident cases= ≈460). The EPIC-InterAct case-cohort study was used to investigate the prospective association between intake of tea and risk of type 2 diabetes (nsubcohort= 16,154; nincident cases= 11,541; eight European countries). To investigate the second objective, the mediating role of CRP in the association between meat, GI, or GL and risk of type 2 diabetes was studied. Furthermore, the cross-sectional associations between a literature-based index that reflects the inflammatory potential of the diet, the Adapted Dietary Inflammatory Index (ADII), and markers of glucose metabolism were investigated in CODAM and Hoorn studies (n= 1,034). In the Rotterdam study, a dietary pattern that relates to CRP was constructed and related to risk of type 2 diabetes. Results Intake of lean fish (Relative Risk (RR)≥23 vs. 0 g/day= 1.30 [95%Confindence Interval (95%CI) 1.01, 1.68]) and intake of processed meat (RR>30 vs. 0 g/day= 1.73 [95%CI 1.16, 2.57]) were associated with a higher risk of type 2 diabetes. The intake of tea was associated with a lower risk of type 2 diabetes (RR≥4 vs. 0 cups/day= 0.84 [95%CI 0.81, 1.00]). No statistically significant associations were observed for the other dietary factors, i.e., proportions of saturated, mono-unsaturated, trans, and poly-unsaturated fatty acids in cholesteryl esters, intake of fatty fish, intake of red meat, intake of poultry, GI, and GL. Our findings showed that the mediating role of CRP in the association between intake of meat, GI, or GL and risk of type 2 diabetes was small. However, the total dietary inflammatory potential of the diet, as estimated by ADII and a pro-inflammatory dietary pattern, were associated with insulin resistance or risk of type 2 diabetes, respectively. Conclusion The findings in this thesis together with results from other studies indicate that high intake of tea and low intake of processed meat can help lower the risk of type 2 diabetes. The findings also suggest that some diets can affect the development of type 2 diabetes through harmful effects on chronic low-grade inflammation. Which combinations of dietary factors cause the pro-inflammatory properties of these diets remains to be determined. </p

Meat consumption, diabetes and its complications

Several prospective studies have reported that risk of type 2 diabetes (T2DM) is elevated in meat consumers, especially when processed meats are consumed. Elevated risks of coronary heart disease (CHD) and stroke in meat consumers have also been reported. In this overview, the evidence regarding meat consumption and the risk of diabetes, both type 1 diabetes (T1DM) and T2DM and their macro- and microvascular complications, is reviewed. For T2DM, we performed a new meta-analysis including publications up to October 2012. For T1DM, only a few studies have reported increased risks for meat consumers or for high intake of saturated fatty acids and nitrates and nitrites. For T2DM, CHD, and stroke, the evidence is strongest. Per 100 g of total meat, the pooled relative risk (RR) for T2DM is 1.15 (95 % CI 1.07–1.24), for (unprocessed) red meat 1.13 (95 % CI 1.03–1.23), and for poultry 1.04 (95 % CI 0.99–1.33); per 50 g of processed meat, the pooled RR is 1.32 (95 % CI 1.19–1.48). Hence, the strongest association regarding T2DM is observed for processed (red) meat. A similar observation has been made for CHD. For stroke, however, a recent meta-analysis shows moderately elevated risks for meat consumers, for processed as well as for fresh meats. For the microvascular complications of diabetes, few prospective data were available, but suggestions for elevated risks can be derived from findings on hyperglycemia and hypertension. The results are discussed in the light of the typical nutrients and other compounds present in meat—that is, saturated and trans fatty acids, dietary cholesterol, protein and amino acids, heme-iron, sodium, nitrites and nitrosamines, and advanced glycation end products. In light of these findings, a diet moderate to low in red meat, unprocessed and lean, and prepared at moderate temperatures is probably the best choice from the public health point of view

The prospective association between total and type of fish intake and type 2 diabetes in 8 European countries: EPIC-InterAct Study

Background: Epidemiologic evidence of an association between fish intake and type 2 diabetes (T2D) is inconsistent and unresolved. Objective: The objective was to examine the association between total and type of fish intake and T2D in 8 European countries. Design: This was a case-cohort study, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, with 3.99 million person-years of follow-up, 12,403 incident diabetes cases, and a random subcohort of 16,835 individuals from 8 European countries. Habitual fish intake (lean fish, fatty fish, total fish, shellfish, and combined fish and shellfish) was assessed by country-specific dietary questionnaires. HRs were estimated in each country by using Prentice-weighted Cox regression models and pooled by using a random-effects meta-analysis. Results: No overall association was found between combined fish and shellfish intake and incident T2D per quartile (adjusted HR: 1.00; 95% CI: 0.94, 1.06; P-trend = 0.99). Total fish, lean fish, and shellfish intakes separately were also not associated with T2D, but fatty fish intake was weakly inversely associated with T2D: adjusted HR per quartile 0.97 (0.94, 1.00), with an HR of 0.84 (0.70, 1.01), 0.85 (0.76, 0.95), and 0.87 (0.78, 0.97) for a comparison of the second, third, and fourth quartiles with the lowest quartile of intake, respectively (P-trend = 0.06). Conclusions: These findings suggest that lean fish, total fish, and shellfish intakes are not associated with incident diabetes but that fatty fish intake may be weakly inversely associated. Replication of these findings in other populations and investigation of the mechanisms underlying these associations are warranted. Meanwhile, current public health recommendations on fish intake should remain unchange

The prospective association between total and type of fish intake and type 2 diabetes in 8 European countries: EPIC-InterAct Study

Background: Epidemiologic evidence of an association between fish intake and type 2 diabetes (T2D) is inconsistent and unresolved. Objective: The objective was to examine the association between total and type of fish intake and T2D in 8 European countries. Design: This was a case-cohort study, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, with 3.99 million person-years of follow-up, 12,403 incident diabetes cases, and a random subcohort of 16,835 individuals from 8 European countries. Habitual fish intake (lean fish, fatty fish, total fish, shellfish, and combined fish and shellfish) was assessed by country-specific dietary questionnaires. HRs were estimated in each country by using Prentice-weighted Cox regression models and pooled by using a random-effects meta-analysis. Results: No overall association was found between combined fish and shellfish intake and incident T2D per quartile (adjusted HR: 1.00; 95% CI: 0.94, 1.06; P-trend = 0.99). Total fish, lean fish, and shellfish intakes separately were also not associated with T2D, but fatty fish intake was weakly inversely associated with T2D: adjusted HR per quartile 0.97 (0.94, 1.00), with an HR of 0.84 (0.70, 1.01), 0.85 (0.76, 0.95), and 0.87 (0.78, 0.97) for a comparison of the second, third, and fourth quartiles with the lowest quartile of intake, respectively (P-trend = 0.06). Conclusions: These findings suggest that lean fish, total fish, and shellfish intakes are not associated with incident diabetes but that fatty fish intake may be weakly inversely associated. Replication of these findings in other populations and investigation of the mechanisms underlying these associations are warranted. Meanwhile, current public health recommendations on fish intake should remain unchange

Comparison of fatty acid proportions in serum cholesteryl esters among people with different glucose tolerance status: The CoDAM study

Background and aim - Altered fatty acid patterns in blood may be associated with insulin resistance and related disorders. We investigated whether serum proportions of cholesteryl fatty acids and desaturase activity are associated with glucose tolerance status and insulin resistance. Methods and results - Data were obtained from a cross-sectional study among 471 Dutch participants aged =40 years. Individual fatty acids in serum cholesteryl esters were determined and endogenous conversions by desaturases were estimated from product-to-precursor ratios. Proportions of fatty acids were compared among participants with normal glucose tolerance, impaired glucose metabolism and newly diagnosed type 2 diabetes. Partial Spearman correlation coefficients between fatty acids and homeostasis model assessment-insulin resistance (HOMA-IR) were calculated. Adjustments were made for lifestyle and nutritional factors. The proportions of total saturated, mono-unsaturated, trans- and poly-unsaturated fatty acids did not differ significantly between groups, but several individual fatty acids did; the proportions of C18:0 and C20:3n6 were higher, whereas those of C18:1n7 and C20:4n6 were lower in participants with type 2 diabetes compared with those with normal glucose tolerance. Activity of ¿5-desaturase, that is, ratio of C20:4n6 to C20:3n6, was lower (p <0.01) in participants with type 2 diabetes (7.4) than with normal glucose tolerance (8.4). HOMA-IR was correlated positively with ¿9-desaturase activity (r = 0.11, p <0.01) and inversely with ¿5-desaturase activity (r = -0.21, p <0.01). Conclusion - The observed lower ¿5-desaturase activity in participants with type 2 diabetes and its inverse association with HOMA-IR suggest that changes in fatty-acid metabolism may play a role in the aetiology of type 2 diabete

Meat consumption and its association with C-reactive protein and incident type 2 diabetes : The Rotterdam Study

OBJECTIVE To investigate whether intake of different types of meat is associated with circulating C-reactive protein (CRP) and risk of type 2 diabetes in a prospective cohort study. RESEARCH DESIGN AND METHODS Our analysis included 4,366 Dutch participants who did not have diabetes at baseline. During a median follow-up period of 12.4 years, 456 diabetes cases were confirmed. Intake of red meat, processed meat, and poultry was derived from a food frequency questionnaire, and their association with serum high-sensitivity CRP was examined cross-sectionally using linear regression models. Their association with risk of type 2 diabetes was examined using multivariate Cox proportional hazards model, including age, sex, family history of diabetes, and lifestyle and dietary factors. RESULTS An increment of 50 g of processed meat was associated with increased CRP concentration (ßprocessed meat = 0.12; P = 0.01), whereas intake of red meat and poultry was not. When comparing the highest to the lowest category of meat intake with respect to diabetes incidence, the adjusted relative risks were as follows: for red meat (1.42 [95% CI 1.06–1.91]), for processed meat (1.87 [1.26–2.78]), and for poultry (0.95 [0.74–1.22]). Additional analysis showed that the associations were not affected appreciably after inclusion of CRP into the model. After adjustment for BMI, however, the association for red meat attenuated to 1.18 (0.88–1.59). CONCLUSIONS Intake of processed meat is associated with higher risk of type 2 diabetes. It appears unlikely that CRP mediates this associatio

Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome

Contains fulltext : 182887.pdf (publisher's version ) (Closed access)Background: Persons with Lynch syndrome (LS) have high lifetime risk of developing colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR) genes. An important process in the development of CRTs is inflammation, which has been shown to be modulated by diet.Objective: We aimed to investigate the association between the inflammatory potential of the diet and the risk of CRTs in persons with LS.Design: We used the dietary intake of 457 persons with LS from a prospective cohort study to calculate the adapted dietary inflammatory index (ADII). The ADII was split into tertiles in which the highest tertile reflects the most proinflammatory potential of the diet. Cox proportional hazard models, with robust sandwich variance estimates to adjust for dependency within families, were used to calculate HRs and 95% CIs of CRTs by ADII tertile. HRs were adjusted for age, smoking status, and education level, and number of colonoscopies as a time-dependent variable. A potential effect measure modification was explored by stratifying the results by mutated MMR gene, sex, and a history of CRTs. We performed sensitivity analyses by repeating the analyses in non-nonsteroidal anti-inflammatory drug (NSAID) users (n = 315).Results: During a median follow-up time of 59 mo, 200 participants (43.8%) developed CRTs. No significant association was shown between highest compared with lowest ADII tertiles (HR for highest compared with lowest tertiles: 1.37; 95% CI: 0.80, 2.34). Stratification by mutated MMR gene, sex, and CRT history did not show significantly differential associations (P-interactions >/= 0.64). In non-NSAID users, an HR of 1.60 (95% CI: 0.88, 2.93) for highest compared with lowest tertiles was shown. No significant effect modification was shown in this group either (P-interactions >/= 0.24).Conclusion: A proinflammatory potential of the diet does not seem to be significantly associated with CRT risk in persons with LS

Meat consumption and its association with C-reactive protein and incident type 2 diabetes: The Rotterdam study

OBJECTIVE - To investigate whether intake of different types of meat is associated with circulating C-reactive protein (CRP) and risk of type 2 diabetes in a prospective cohort study. RESEARCH DESIGN AND METHODS - Our analysis included 4,366 Dutch participants who did not have diabetes at baseline. During a median follow-up period of 12.4 years, 456 diabetes cases were confirmed. Intake of red meat, processed meat, and poultry was derived from a food frequency questionnaire, and their association with serum high-sensitivity CRP was examined cross-sectionally using linear regression models. Their association with risk of type 2 diabetes was examined using multivariate Cox proportional hazards model, including age, sex, family history of diabetes, and lifestyle and dietary factors. RESULTS - An increment of 50 g of processed meat was associated with increased CRP concentration (β processed meat = 0.12; P = 0.01), whereas intake of red meat and poultry was not. When comparing the highest to the lowest category of meat intake with respect to diabetes incidence, the adjusted relative risks were as follows: for red meat (1.42 [95% CI 1.06-1.91]), for processed meat (1.87 [1.26-2.78]), and for poultry (0.95 [0.74-1.22]). Additional analysis showed tha

Adapted dietary inflammatory index and its association with a summary score for low-grade inflammation and markers of glucose metabolism: the Cohort study on Diabetes and Atherosclerosis Maastricht (CODAM) and the Hoorn study

Background: Diet may be associated with the development of type 2 diabetes through its effects on low-grade inflammation. Objectives: We investigated whether an adapted dietary inflammatory index (ADII) is associated with a summary score for low-grade inflammation and markers of glucose metabolism. In addition, we investigated the mediating role of inflammation in the association between ADII and markers of glucose metabolism. Design: We performed cross-sectional analyses of 2 Dutch cohort studies (n= 1024). An ADII was obtained by multiplying standardized energy-adjusted intakes of dietary components by literature-based dietary inflammatory weights that reflected the inflammatory potential of components. Subsequently, these multiplications were summed. Six biomarkers of inflammation were compiled in a summary score. Associations of the ADII (expressed per SD) with the summary score for inflammation and markers of glucose metabolism were investigated by using multiple linear regression models. Inflammation was considered a potential mediator in the analysis with markers of glucose metabolism. Results: A higher ADII was associated with a higher summary score for inflammation [beta-adjusted = 0.04 per SD (95% CI: 0.01, 0.07 per SD)]. The ADII was, also adversely associated with insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR): beta-adjusted = 3.5% per SD (95% CI: 0.6%, 6.-3% per SD)]. This association was attenuated after the inclusion of the summary score for inflammation [beta-adjusted+inflammation = 2.2% (95% CI: -0.6%, 5.0%)]. The ADII was also adversely associated with fasting glucose and postload glucose but not with glycated hemoglobin. Conclusion: The significant mediating role of low-grade inflammation in the association between the ADII and HOMA-IR suggests that inflammation might be one of the pathways through which diet affects insulin resistance